chr19-35743863-C-T

Variant names:

• chr19-35743863-C-T
• rs760072842
• NM_001040425.3:c.407G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040425.3(U2AF1L4):​c.407G>A​(p.Arg136Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,461,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: U2AF1L4 NM_001040425.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.726
• Publications: 2 publications found

Genes affected

U2AF1L4 (HGNC:23020): (U2 small nuclear RNA auxiliary factor 1 like 4) Predicted to enable pre-mRNA 3'-splice site binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be part of U2AF complex and spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267120 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05508709).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040425.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1L4	NM_001040425.3	MANE Select	c.407G>A	p.Arg136Gln	missense	Exon 5 of 6	NP_001035515.1	Q8WU68-3
	U2AF1L4	NM_144987.4		c.349G>A	p.Gly117Ser	missense	Exon 5 of 6	NP_659424.2	Q8WU68-2
	U2AF1L4	NM_001369824.2		c.349G>A	p.Gly117Ser	missense	Exon 5 of 6	NP_001356753.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	U2AF1L4	ENST00000378975.8	TSL:1 MANE Select	c.407G>A	p.Arg136Gln	missense	Exon 5 of 6	ENSP00000368258.2	Q8WU68-3
	U2AF1L4	ENST00000292879.9	TSL:1	c.349G>A	p.Gly117Ser	missense	Exon 5 of 6	ENSP00000292879.4	Q8WU68-2
	U2AF1L4	ENST00000587987.5	TSL:1	n.*375G>A		non_coding_transcript_exon	Exon 6 of 8	ENSP00000465170.1	K7EJH3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249636 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1461346 Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 15 AN XY: 726940

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.95
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.73
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.056
Sift	Benign	0.48	T
Sift4G	Benign	0.17	T
Polyphen		0.74	P
Vest4		0.28
MutPred		0.34		Gain of glycosylation at G117 (P = 0.0529)
MVP		0.048
MPC		0.16
ClinPred		0.24	T
GERP RS		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.31
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs760072842; hg19: chr19-36234764; COSMIC: COSV53073669; COSMIC: COSV53073669;